Development and Functional Evaluation of MDR1-expressing Microvascular Endothelial-like Cells Derived from Human iPS Cells as an In vitro Blood-brain Barrier Model.

In order to establish an in vitro model of the human blood-brain barrier (BBB), MDR1-overexpressing human induced pluripotent stem cells (hiPSCs) were generated, and they were differentiated to MDR1-expressing brain microvascular endothelial-like cells (MDR1-expressing hiPS-BMECs). MDR1-expressing hiPS-BMECs monolayers showed good barrier function in terms of tight junction protein expression and trans-epithelial electrical resistance (TEER). In sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS), MDR1 protein expression was markedly increased in MDR1-expressing hiPS-BMECs, whereas other ABC and SLC transporters showed almost identical expression between MDR1-expressing hiPS-BMECs and mock hiPS-BMECs, suggesting that MDR1 overexpression had little or no knock-on effect on other proteins.

Inhibition of Glycogen Synthase Kinase 3ß Enhances Functions of Induced Pluripotent Stem Cell-Derived Brain Microvascular Endothelial Cells in the Blood-Brain Barrier.

Brain microvascular endothelial cells (BMECs) are essential component of the blood-brain barrier (BBB). BMECs strictly regulate the entry of various molecules into the central nervous system from the peripheral circulation by forming tight junctions and expressing various influx/efflux transporters and receptors. In vitro BBB models have been widely reported with primary BMECs isolated from animals, although it is known that the expression patterns and levels of transporters and receptors in BMECs differ between humans and animals.

Effect of heat stress on blood-brain barrier integrity in iPS cell-derived microvascular endothelial cell models.

The incidence of heatstroke has been increasing. Heatstroke has been shown to affect physiological barrier functions. However, there are few studies of the effect of heat stress on the blood-brain barrier (BBB) function.

Wnt--Catenin Signaling Promotes the Maturation of Mast Cells.

Mast cells play an important role in the pathogenesis of allergic diseases. Immature mast cells migrate into peripheral tissues from the bone marrow and undergo complete maturation. Interestingly, mast cells have characteristics similar to hematopoietic stem cells (HSCs), such as self-renewal and c-kit expression.

Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb.

Exogenous retinoic acid (RA) induces marked effects on limb patterning, but the precise role of endogenous RA in this process has remained unknown. We have studied the role of RA in mouse limb development by focusing on CYP26B1, a cytochrome P450 enzyme that inactivates RA. Cyp26b1 was shown to be expressed in the distal region of the developing limb bud, and mice that lack CYP26B1 exhibited severe limb malformation (meromelia).